Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimens

Using a synthetic peptide substrate, tyrosine protein kinase (TPK) activity was measured in 21 tumors from patients with histologically confirmed breast cancer and in five normal breast tissues from patients undergoing reduction mammoplasty. In 20 of 21 cancer specimens, tumor was available to assess phosphotyrosine (PT) immunohistochemically. Breast cancer specimens possessed significantly more TPK activity than normal breast tissues (Cancer = 43.9 +/- 3.1 pm/mg protein/min, [Mean +/- S.E.M.]; Normal = 3.4 +/- 0.9, p < 0.001). TPK activity was higher in the clinically more aggressive infiltrating ductal cancers compared to the less aggressive intraductal cancers (Infiltrating = 55.9 +/- 5.8; Intraductal = 17.2 +/- 3.4, p < 0.01). TPK activity in tumors with both infiltrating and intraductal histology was intermediate (34.0 +/- 7.2). Significant correlation existed between membrane TPK enzymatic activity and PT expression by immunohistochemistry. There was no relationship between estrogen or progesterone receptor status and TPK activity or PT; however, TPK activity from node negative breast cancer tissue was significantly less than from node positive specimens (p < 0.01). We conclude that breast cancer specimens possess elevated amounts of TPK which correlate with PT expression, and that increased tyrosine phosphorylation appears to correlate with the biologic aggressiveness of the malignant tumor.